Macrophages and platelets are the major source of protease nexin-1 in human atherosclerotic plaque
Macrophages and platelets are the major source of protease nexin-1 in human atherosclerotic plaque
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DOI：
10.1161/atvbaha.108.171389
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发表时间：
2008-10-01
影响因子：
8.7
通讯作者：
Bouton, Marie-Christine
中科院分区：
文献类型：
--
作者：
Mansilla, Silvana;Boulaftali, Yacine;Bouton, Marie-Christine
β-蛋白酶连接蛋白-1（PN-1）是一种由血管平滑肌细胞和内皮细胞组成性表达的丝氨酸蛋白酶抑制剂，抑制凝血酶、纤溶酶原激活剂和纤溶酶，因此可以预期在血管生物学中发挥作用。本研究解决的问题PN-1的表达在人类atherothrombosis.Methods和结果免疫组织化学和生物化学研究证实，PN-1在正常人动脉的中层中表达在中等水平，并表明PN-1的表达增加动脉粥样硬化血栓病变。在早期非复杂斑块中，PN-1与浸润的单核细胞相关。在晚期病变中观察到强PN-1信号，主要是在斑块内血管相关结构中。单核细胞/巨噬细胞和血小板被确定为动脉粥样硬化血栓形成物质中PN-1的主要来源。分离的人单核细胞和血小板都表达高水平的活性PN-1，单核细胞PN-1的表达上调，在信使和蛋白质水平，响应于刺激的脂多糖。相反，PN-1的表达在其分化为巨噬细胞的过程中被下调，巨噬细胞被证明产生降解形式的PN-1。结论血小板和单核细胞/巨噬细胞是人动脉粥样硬化血栓斑块中PN-1的主要来源。因此，PN-1可能代表动脉粥样硬化病变演变中的一个新因素。
Objective-Protease nexin-1 (PN-1), a serpin constitutively expressed by vascular smooth muscle cells and endothelial cells, inhibits thrombin, plasminogen activators, and plasmin and can thus be expected to play a role in vascular biology. The present study addressed the question of PN-1 expression in human atherothrombosis.Methods and Results-Immunohistochemistry and biochemical studies confirmed that PN-1 was expressed at a moderate level in the medial layer of normal human arteries and showed that PN-1 expression was increased in atherothrombotic lesions. In early noncomplicated plaques, PN-1 was associated with infiltrating mononuclear cells. A strong PN-1 signal was observed in advanced lesions, principally in intraplaque hemorrhage-related structures. Monocytes/ macrophages and platelets were identified as the main sources of PN-1 within atherothrombotic material. Isolated human monocytes and platelets both expressed high levels of active PN-1, and monocyte PN-1 expression was upregulated, at both messenger and protein levels, in response to stimulation by lipopolysaccharides. In contrast, PN-1 expression was downregulated during their differentiation into macrophages which were shown to produce degraded forms of PN-1.Conclusions-Platelets and monocytes/ macrophages are a major source of PN-1 in human atherothrombotic plaques. PN-1 could thus represent a new actor in the evolution of atherosclerotic lesions.